There is an increasing need for alternative dosage forms to conventional tablets and capsules. Such alternative dosage forms are, for example, in the form of small particles which can be sprinkled onto food or mixed with liquids to form a suspension that can be readily swallowed. These dosage forms provide improved patient compliance, particularly in patients who exhibit difficulties swallowing conventional dosage forms such as pediatric and geriatric patients, subjects who suffer from impaired swallowing and subjects who suffer from psychiatric disorders.
Formulations suitable for forming suspensions prior to administration are advantageous compared to ready-to-use suspensions, mainly due to their improved stability in storage conditions. A problem that is often encountered with ready-to-use suspensions is the sedimentation or segregation of some of the particles which result in a non-uniform distribution of the active compound. Another problem occurs when the suspension is becoming too viscous thereby being incompatible for oral administration as well as for administration through a nasogastric tube.
Proton pump inhibitors (PPIs) are potent inhibitors of gastric acid secretion by specific inhibition of the H+/K+-ATPase enzyme system at the secretory surface of the gastric parietal cells. They are used for the treatment of gastric and duodenal ulcers, gastroesophageal reflux disease and other excessive gastrointestinal acid secretory disorders. PPIs are typically benzimidazole derivatives such as omeprazole, lansoprazole, and pantoprazole. U.S. Pat. Nos. 4,045,563; 4,255,431; 4,359,465; 4,472,409; 4,508,905; 4,628,098; 4,738,975; 4,786,505; 4,853,230; 5,045,321; 5,045,552; and 5,312,824 disclose benzimidazole compounds which can be used as proton pump inhibitors and compositions comprising same.
WO 2006/068596 describes a solid oral pharmaceutical dosage form comprising: (a) a multitude of enteric coated pellets, wherein each enteric coated pellet comprises an acid sensitive proton pump inhibitor, and (b) a suspension modifying granulate comprising a rapidly dissolving diluent, a gelling agent which is a xanthan gum, an acidic pH-regulating agent, a binder, and optionally, a disintegrant, wherein the dosage form is a rapidly-gelling granulate mixture, with the proviso that the granulate is free from bicarbonate and carbonate salts.
EP 1949900 describes a controlled release formulation of solid products for oral administration adapted for preparing single dose sachets, comprising very little pellets with controlled and/or retarded release, consisting of inert granules with size between 250 and 600 μm, covered with an active ingredient having a size between 1 and 200 μm, in turn covered by a membrane adapted to give the controlled release, to obtain pellets for direct administration having a final size between 425 and 710 μm.
EP 1232746 describes readily suspendible dry powder mixture composition comprising a gellant or thickener, comprising at least one xanthan gum having a specific particle size distribution, a filler, a wetting agent or surfactant, and a pharmacologically active substance. EP 1232746 further describes the use of the dry powder mixture composition for the preparation of a suspension of the active substance and to liquid or semi-liquid pharmaceutical compositions comprising a suspension of an active substance.
WO 2004/004690 describes a liquid dosage form having enteric coated microgranules comprising an acid-labile drug and a liquid suspension having a pH less than 6.0 and a viscosity sufficient to suspend the microgranules. Carbonates or bicarbonates may be used in the dosage forms.
There is an unmet need for a PPI composition in the form of small particles which is suitable for forming a viscous suspension upon admixing with a liquid for oral administration.